ID TM216_HUMAN Reviewed; 145 AA. AC Q9P0N5; A8MZ23; B7Z8N1; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2012, sequence version 3. DT 24-JAN-2024, entry version 146. DE RecName: Full=Transmembrane protein 216; GN Name=TMEM216; ORFNames=HSPC244; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP IDENTIFICATION IN THE TECTONIC-LIKE COMPLEX, AND INTERACTION WITH TMEM107. RX PubMed=26595381; DOI=10.1038/ncb3273; RA Lambacher N.J., Bruel A.L., van Dam T.J., Szymanska K., Slaats G.G., RA Kuhns S., McManus G.J., Kennedy J.E., Gaff K., Wu K.M., van der Lee R., RA Burglen L., Doummar D., Riviere J.B., Faivre L., Attie-Bitach T., RA Saunier S., Curd A., Peckham M., Giles R.H., Johnson C.A., Huynen M.A., RA Thauvin-Robinet C., Blacque O.E.; RT "TMEM107 recruits ciliopathy proteins to subdomains of the ciliary RT transition zone and causes Joubert syndrome."; RL Nat. Cell Biol. 18:122-131(2016). RN [7] RP VARIANT JBTS2 LEU-73. RX PubMed=20036350; DOI=10.1016/j.ajhg.2009.12.007; RA Edvardson S., Shaag A., Zenvirt S., Erlich Y., Hannon G.J., Shanske A.L., RA Gomori J.M., Ekstein J., Elpeleg O.; RT "Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 RT mutation."; RL Am. J. Hum. Genet. 86:93-97(2010). RN [8] RP VARIANTS MKS2 HIS-73; ALA-77 AND ARG-114, AND VARIANTS JBTS2 CYS-73; HIS-73 RP AND LEU-73. RX PubMed=20512146; DOI=10.1038/ng.594; RA Valente E.M., Logan C.V., Mougou-Zerelli S., Lee J.H., Silhavy J.L., RA Brancati F., Iannicelli M., Travaglini L., Romani S., Illi B., Adams M., RA Szymanska K., Mazzotta A., Lee J.E., Tolentino J.C., Swistun D., RA Salpietro C.D., Fede C., Gabriel S., Russ C., Cibulskis K., Sougnez C., RA Hildebrandt F., Otto E.A., Held S., Diplas B.H., Davis E.E., Mikula M., RA Strom C.M., Ben-Zeev B., Lev D., Sagie T.L., Michelson M., Yaron Y., RA Krause A., Boltshauser E., Elkhartoufi N., Roume J., Shalev S., Munnich A., RA Saunier S., Inglehearn C., Saad A., Alkindy A., Thomas S., Vekemans M., RA Dallapiccola B., Katsanis N., Johnson C.A., Attie-Bitach T., Gleeson J.G.; RT "Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and RT related syndromes."; RL Nat. Genet. 42:619-625(2010). RN [9] RP VARIANT JBTS2 PHE-89. RX PubMed=22425360; DOI=10.1016/j.ajhg.2012.02.011; RA Srour M., Schwartzentruber J., Hamdan F.F., Ospina L.H., Patry L., RA Labuda D., Massicotte C., Dobrzeniecka S., Capo-Chichi J.M., RA Papillon-Cavanagh S., Samuels M.E., Boycott K.M., Shevell M.I., RA Laframboise R., Desilets V., Maranda B., Rouleau G.A., Majewski J., RA Michaud J.L.; RT "Mutations in C5ORF42 cause Joubert syndrome in the French Canadian RT population."; RL Am. J. Hum. Genet. 90:693-700(2012). RN [10] RP VARIANTS JBTS2 CYS-73; HIS-73 AND LEU-73, FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=22282472; DOI=10.1126/science.1213506; RA Lee J.H., Silhavy J.L., Lee J.E., Al-Gazali L., Thomas S., Davis E.E., RA Bielas S.L., Hill K.J., Iannicelli M., Brancati F., Gabriel S.B., Russ C., RA Logan C.V., Sharif S.M., Bennett C.P., Abe M., Hildebrandt F., Diplas B.H., RA Attie-Bitach T., Katsanis N., Rajab A., Koul R., Sztriha L., Waters E.R., RA Ferro-Novick S., Woods G.C., Johnson C.A., Valente E.M., Zaki M.S., RA Gleeson J.G.; RT "Evolutionarily assembled cis-regulatory module at a human ciliopathy RT locus."; RL Science 335:966-969(2012). CC -!- FUNCTION: Part of the tectonic-like complex which is required for CC tissue-specific ciliogenesis and may regulate ciliary membrane CC composition. {ECO:0000269|PubMed:22282472}. CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex). CC Interacts with TMEM107. {ECO:0000269|PubMed:26595381}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane CC protein {ECO:0000305}. Cytoplasm, cytoskeleton, cilium basal body CC {ECO:0000269|PubMed:22282472}. Note=Localizes at the transition zone, a CC region between the basal body and the ciliary axoneme. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9P0N5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9P0N5-2; Sequence=VSP_040295, VSP_040296; CC Name=3; CC IsoId=Q9P0N5-3; Sequence=VSP_040296; CC -!- DISEASE: Joubert syndrome 2 (JBTS2) [MIM:608091]: A disorder presenting CC with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal CC breathing abnormalities and psychomotor delay. Neuroradiologically, it CC is characterized by cerebellar vermian hypoplasia/aplasia, thickened CC and reoriented superior cerebellar peduncles, and an abnormally large CC interpeduncular fossa, giving the appearance of a molar tooth on CC transaxial slices (molar tooth sign). Additional variable features CC include retinal dystrophy and renal disease. CC {ECO:0000269|PubMed:20036350, ECO:0000269|PubMed:20512146, CC ECO:0000269|PubMed:22282472, ECO:0000269|PubMed:22425360}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Meckel syndrome 2 (MKS2) [MIM:603194]: A disorder CC characterized by a combination of renal cysts and variably associated CC features including developmental anomalies of the central nervous CC system (typically encephalocele), hepatic ductal dysplasia and cysts, CC and polydactyly. {ECO:0000269|PubMed:20512146}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: TMEM138 and TMEM216 genes are adjacent and are aligned CC in a head-to-tail configuration. They share some cis regulatory region CC and display coordinated expression. Genes were joined by chromosomal CC rearrangement at the amphiboan to reptile evolutionary transition CC around 340 million years ago (PubMed:22282472). CC {ECO:0000305|PubMed:22282472}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF151078; AAF36164.1; -; mRNA. DR EMBL; AK303687; BAH14017.1; -; mRNA. DR EMBL; CR457166; CAG33447.1; -; mRNA. DR EMBL; AP003108; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC011010; AAH11010.1; -; mRNA. DR CCDS; CCDS53640.1; -. [Q9P0N5-1] DR CCDS; CCDS86205.1; -. [Q9P0N5-3] DR RefSeq; NP_001167461.1; NM_001173990.2. [Q9P0N5-1] DR RefSeq; NP_001167462.1; NM_001173991.2. [Q9P0N5-3] DR RefSeq; NP_001317214.1; NM_001330285.1. DR RefSeq; NP_057583.2; NM_016499.5. [Q9P0N5-2] DR RefSeq; XP_005274096.1; XM_005274039.3. DR AlphaFoldDB; Q9P0N5; -. DR SMR; Q9P0N5; -. DR BioGRID; 119415; 245. DR ComplexPortal; CPX-2531; MKS transition zone complex. DR DIP; DIP-61992N; -. DR IntAct; Q9P0N5; 243. DR STRING; 9606.ENSP00000334844; -. DR BioMuta; TMEM216; -. DR DMDM; 380865448; -. DR PaxDb; 9606-ENSP00000440638; -. DR PeptideAtlas; Q9P0N5; -. DR ProteomicsDB; 83583; -. [Q9P0N5-2] DR DNASU; 51259; -. DR Ensembl; ENST00000334888.10; ENSP00000334844.5; ENSG00000187049.11. [Q9P0N5-3] DR Ensembl; ENST00000515837.7; ENSP00000440638.1; ENSG00000187049.11. [Q9P0N5-1] DR GeneID; 51259; -. DR KEGG; hsa:51259; -. DR MANE-Select; ENST00000515837.7; ENSP00000440638.1; NM_001173990.3; NP_001167461.1. DR UCSC; uc010rlj.3; human. [Q9P0N5-1] DR AGR; HGNC:25018; -. DR CTD; 51259; -. DR DisGeNET; 51259; -. DR GeneCards; TMEM216; -. DR GeneReviews; TMEM216; -. DR HGNC; HGNC:25018; TMEM216. DR HPA; ENSG00000187049; Low tissue specificity. DR MalaCards; TMEM216; -. DR MIM; 603194; phenotype. DR MIM; 608091; phenotype. DR MIM; 613277; gene. DR neXtProt; NX_Q9P0N5; -. DR OpenTargets; ENSG00000187049; -. DR Orphanet; 2318; Joubert syndrome with oculorenal defect. DR Orphanet; 564; Meckel syndrome. DR Orphanet; 2754; Orofaciodigital syndrome type 6. DR PharmGKB; PA162406553; -. DR VEuPathDB; HostDB:ENSG00000187049; -. DR eggNOG; KOG4502; Eukaryota. DR GeneTree; ENSGT00940000153899; -. DR HOGENOM; CLU_135948_0_0_1; -. DR InParanoid; Q9P0N5; -. DR OMA; AEILMFV; -. DR OrthoDB; 313556at2759; -. DR TreeFam; TF323824; -. DR PathwayCommons; Q9P0N5; -. DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. DR SignaLink; Q9P0N5; -. DR BioGRID-ORCS; 51259; 22 hits in 1161 CRISPR screens. DR ChiTaRS; TMEM216; human. DR GeneWiki; TMEM216; -. DR GenomeRNAi; 51259; -. DR Pharos; Q9P0N5; Tbio. DR PRO; PR:Q9P0N5; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q9P0N5; Protein. DR Bgee; ENSG00000187049; Expressed in primordial germ cell in gonad and 174 other cell types or tissues. DR ExpressionAtlas; Q9P0N5; baseline and differential. DR GO; GO:0035869; C:ciliary transition zone; IBA:GO_Central. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0036038; C:MKS complex; ISS:UniProtKB. DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB. DR GO; GO:1905515; P:non-motile cilium assembly; IBA:GO_Central. DR InterPro; IPR019184; Uncharacterised_TM-17. DR PANTHER; PTHR13531; GEO07735P1-RELATED-RELATED; 1. DR PANTHER; PTHR13531:SF5; TRANSMEMBRANE PROTEIN 216; 1. DR Pfam; PF09799; Transmemb_17; 1. DR Genevisible; Q9P0N5; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell projection; Ciliopathy; KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Disease variant; KW Joubert syndrome; Meckel syndrome; Membrane; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..145 FT /note="Transmembrane protein 216" FT /id="PRO_0000318955" FT TRANSMEM 22..42 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 56..76 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 89..109 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 122..142 FT /note="Helical" FT /evidence="ECO:0000255" FT VAR_SEQ 1..61 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11042152, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3" FT /id="VSP_040295" FT VAR_SEQ 144..145 FT /note="RI -> SMDRI (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11042152, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3" FT /id="VSP_040296" FT VARIANT 73 FT /note="R -> C (in JBTS2; dbSNP:rs779526456)" FT /evidence="ECO:0000269|PubMed:20512146, FT ECO:0000269|PubMed:22282472" FT /id="VAR_064028" FT VARIANT 73 FT /note="R -> H (in JBTS2 and MKS2; dbSNP:rs201108965)" FT /evidence="ECO:0000269|PubMed:20512146, FT ECO:0000269|PubMed:22282472" FT /id="VAR_064029" FT VARIANT 73 FT /note="R -> L (in JBTS2; dbSNP:rs201108965)" FT /evidence="ECO:0000269|PubMed:20036350, FT ECO:0000269|PubMed:20512146, ECO:0000269|PubMed:22282472" FT /id="VAR_063388" FT VARIANT 77 FT /note="G -> A (in MKS2; dbSNP:rs386833830)" FT /evidence="ECO:0000269|PubMed:20512146" FT /id="VAR_064030" FT VARIANT 89 FT /note="L -> F (in JBTS2; dbSNP:rs780098806)" FT /evidence="ECO:0000269|PubMed:22425360" FT /id="VAR_068170" FT VARIANT 114 FT /note="L -> R (in MKS2; dbSNP:rs386833831)" FT /evidence="ECO:0000269|PubMed:20512146" FT /id="VAR_064031" FT CONFLICT Q9P0N5-2:86 FT /note="R -> T (in Ref. 1; AAF36164, 3; CAG33447 and 5; FT AAH11010)" FT /evidence="ECO:0000305" FT CONFLICT Q9P0N5-3:147 FT /note="R -> T (in Ref. 1; AAF36164, 3; CAG33447 and 5; FT AAH11010)" FT /evidence="ECO:0000305" SQ SEQUENCE 145 AA; 16487 MW; 0F5024FB2B96D6CB CRC64; MLPRGLKMAP RGKRLSSTPL EILFFLNGWY NATYFLLELF IFLYKGVLLP YPTANLVLDV VMLLLYLGIE VIRLFFGTKG NLCQRKMPLS ISVALTFPSA MMASYYLLLQ TYVLRLEAIM NGILLFFCGS ELLLEVLTLA AFSRI //